scholarly journals Gpa2, a G-Protein α Subunit Required for Hyphal Development in Candida albicans

2002 ◽  
Vol 1 (6) ◽  
pp. 865-874 ◽  
Author(s):  
Cristina Sánchez-Martínez ◽  
José Pérez-Martín
Keyword(s):  
Candida Albicans ◽  
G Protein ◽  
Environmental Changes ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Loss Of Function ◽  
Α Subunit ◽  
Environmental Signals ◽  
G Protein Α Subunit

ABSTRACT Candida albicans is able to respond to environmental changes by inducing a distinct morphological program, which is related to the ability to infect mammalian hosts. Although some of the signal transduction pathways involved in this response are known, it is not clear how the environmental signals are sensed and transmitted to these transduction cascades. In this work, we have studied the function of GPA2, a new gene from C. albicans, which encodes a G-protein α-subunit homologue. We demonstrate that Gpa2 plays an important role in the yeast-hypha dimorphic transition in the response of C. albicans to some environmental inducers. Deletion of both alleles of the GPA2 gene causes in vitro defects in morphological transitions in Spider medium and SLAD medium and in embedded conditions but not in medium containing serum. These defects cannot be reversed by exogenous addition of cyclic AMP. However, overexpression of HST7, which encodes a component of the filament-inducing mitogen-activated protein kinase (MAPK) cascade, bypasses the Gpa2 requirement. We have obtained different gain-of-function and loss-of-function mutant alleles of the GPA2 gene, which we have introduced in several C. albicans genetic backgrounds. Our results indicate that, in response to environmental cues, Gpa2 is required for the regulation of a MAPK signaling pathway.

scholarly journals A New Multisystem Disorder Caused by the Gαs Mutation p.F376V

2018 ◽  
Vol 104 (4) ◽  
pp. 1079-1089 ◽  
Author(s):  
Heike Biebermann ◽  
Gunnar Kleinau ◽  
Dirk Schnabel ◽  
Detlef Bockenhauer ◽  
Louise C Wilson ◽  
...  
Keyword(s):  
G Protein ◽  
De Novo ◽  
Clinical Findings ◽  
New Combination ◽  
Loss Of Function ◽  
Multisystem Disorder ◽  
Gain Of Function ◽  
Α Subunit ◽  
Serum Pth

Abstract Context The α subunit of the stimulatory G protein (Gαs) links numerous receptors to adenylyl cyclase. Gαs, encoded by GNAS, is expressed predominantly from the maternal allele in certain tissues. Thus, maternal heterozygous loss-of-function mutations cause hormonal resistance, as in pseudohypoparathyroidism type Ia, whereas somatic gain-of-function mutations cause hormone-independent endocrine stimulation, as in McCune-Albright syndrome. Objective We report two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Design and Setting Clinical features were studied and sequencing of GNAS was performed. Signaling capacities of wild-type and mutant Gαs were determined in the presence of different G protein–coupled receptors (GPCRs) under basal and agonist-stimulated conditions. Results Both unrelated patients presented with unexplained hyponatremia in infancy, followed by severe early onset gonadotrophin-independent precocious puberty and skeletal abnormalities. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients; this resulted in a clinical phenotype that differed from known Gαs-related diseases and suggested gain of function at the vasopressin 2 receptor (V2R) and lutropin/choriogonadotropin receptor (LHCGR), yet increased serum PTH concentrations indicative of impaired proximal tubular PTH1 receptor (PTH1R) function. In vitro studies demonstrated that Gαs-F376V enhanced ligand-independent signaling at the PTH1R, LHCGR, and V2R and, at the same time, blunted ligand-dependent responses. Structural homology modeling suggested mutation-induced modifications at the C-terminal α5 helix of Gαs that are relevant for interaction with GPCRs and signal transduction. Conclusions The Gαs p.F376V mutation causes a previously unrecognized multisystem disorder.

Loss-of-function mutations identified in the Helical domain of the G protein α-subunit, Gα2, of Dictyostelium discoideum

2005 ◽  
Vol 1722 (3) ◽  
pp. 262-270 ◽  
Author(s):  
Robert E. Gundersen ◽  
Jianxin You ◽  
Steven Rauch ◽  
Kate Farnham ◽  
Christopher McCarty ◽  
...  
Keyword(s):  
G Protein ◽  
Dictyostelium Discoideum ◽  
Loss Of Function ◽  
Α Subunit ◽  
Helical Domain ◽  
G Protein Α Subunit

scholarly journals Host-Induced Gene Silencing of a G Protein α Subunit Gene CsGpa1 Involved in Pathogen Appressoria Formation and Virulence Improves Tobacco Resistance to Ciboria shiraiana

2021 ◽  
Vol 7 (12) ◽  
pp. 1053
Author(s):  
Panpan Zhu ◽  
Shuai Zhang ◽  
Ruolan Li ◽  
Changying Liu ◽  
Wei Fan ◽  
...  
Keyword(s):  
Gene Silencing ◽  
G Protein ◽  
Hyphal Growth ◽  
Fungal Resistance ◽  
Mitogen Activated Protein Kinase ◽  
Plant Tolerance ◽  
Α Subunit ◽  
Oxidative Stresses ◽  
G Protein Α Subunit ◽  
Appressoria Formation

Hypertrophy sorosis scleroteniosis caused by Ciboria shiraiana is the most devastating disease of mulberry fruit. However, few mulberry lines show any resistance to C. shiraiana. An increasing amount of research has shown that host-induced gene silencing (HIGS) is an effective strategy for enhancing plant tolerance to pathogens by silencing genes required for their pathogenicity. In this study, two G protein α subunit genes, CsGPA1 and CsGPA2, were identified from C. shiraiana. Silencing CsGPA1 and CsGPA2 had no effect on hyphal growth but reduced the number of sclerotia and increased the single sclerotium weight. Moreover, silencing CsGpa1 resulted in increased fungal resistance to osmotic and oxidative stresses. Compared with wild-type and empty vector strains, the number of appressoria was clearly lower in CsGPA1-silenced strains. Importantly, infection assays revealed that the virulence of CsGPA1-silenced strains was significantly reduced, which was accompanied by formation of fewer appressoria and decreased expression of several cAMP/PKA- or mitogen-activated protein-kinase-related genes. Additionally, transgenic Nicotiana benthamiana expressing double-stranded RNA targeted to CsGpa1 through the HIGS method significantly improved resistance to C. shiraiana. Our results indicate that CsGpa1 is an important regulator in appressoria formation and the pathogenicity of C. shiraiana. CsGpa1 is an efficient target to improve tolerance to C. shiraiana using HIGS technology.

scholarly journals Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection

2019 ◽  
Vol 220 (9) ◽  
pp. 1477-1488 ◽  
Author(s):  
Marc Swidergall ◽  
Mina Khalaji ◽  
Norma V Solis ◽  
David L Moyes ◽  
Rebecca A Drummond ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mapk Signaling ◽  
Neutrophil Recruitment ◽  
Mononuclear Phagocytes ◽  
Mitogen Activated Protein Kinase ◽  
Vaginal Infections ◽  
Fungal Virulence ◽  
Mitogen Activated Protein

AbstractBackgroundCandidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown.MethodsIn this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro.ResultsCandidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection.ConclusionsThe data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections.

scholarly journals Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus

2021 ◽  
Vol 7 (6) ◽  
pp. 482
Author(s):  
Elisa Gómez-Gil ◽  
Alejandro Franco ◽  
Beatriz Vázquez-Marín ◽  
Francisco Prieto-Ruiz ◽  
Armando Pérez-Díaz ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Environmental Changes ◽  
Yeast Species ◽  
Mapk Signaling ◽  
Fine Tuning ◽  
Mitogen Activated Protein Kinase ◽  
Major Influence ◽  
Cell Integrity ◽  
Mitogen Activated Protein ◽  
Functional Features

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

scholarly journals Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1343
Author(s):  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Vishnu Raj ◽  
Abdullah T. Alhassani ◽  
Ahmad S. Alhassani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activity Index ◽  
Nigella Sativa ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ppar Γ ◽  
Anti Inflammatory ◽  
Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

scholarly journals The G-Protein α-Subunit GasC Plays a Major Role in Germination in the Dimorphic FungusPenicillium marneffei

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 487-499 ◽  
Author(s):  
Sophie Zuber ◽  
Michael J Hynes ◽  
Alex Andrianopoulos
Keyword(s):  
G Protein ◽  
Germination Rate ◽  
Yeast Cells ◽  
Class Iii ◽  
Temperature Dependent ◽  
Gene Encoding ◽  
Α Subunit ◽  
G Protein Α Subunit ◽  
Opportunistic Human Pathogen

AbstractThe opportunistic human pathogen Penicillium marneffei exhibits a temperature-dependent dimorphic switch. At 25°, multinucleate, septate hyphae that can undergo differentiation to produce asexual spores (conidia) are produced. At 37° hyphae undergo arthroconidiation to produce uninucleate yeast cells that divide by fission. This work describes the cloning of the P. marneffei gasC gene encoding a G-protein α-subunit that shows high homology to members of the class III fungal Gα-subunits. Characterization of a ΔgasC mutant and strains carrying a dominant-activating gasCG45R or a dominant-interfering gasCG207R allele show that GasC is a crucial regulator of germination. A ΔgasC mutant is severely delayed in germination, whereas strains carrying a dominant-activating gasCG45R allele show a significantly accelerated germination rate. Additionally, GasC signaling positively affects the production of the red pigment by P. marneffei at 25° and negatively affects the onset of conidiation and the conidial yield, showing that GasC function overlaps with functions of the previously described Gα-subunit GasA. In contrast to the S. cerevisiae ortholog Gpa2, our data indicate that GasC is not involved in carbon or nitrogen source sensing and plays no major role in either hyphal or yeast growth or in the switch between these two forms.

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